ME-344 in Early HER2-negative Breast Cancer With Antiangiogenic-induced Mitochondrial Metabolism

Sponsor
Centro Nacional de Investigaciones Oncologicas CARLOS III
Study ID
NCT02806817
Phase
EARLY_PHASE1
Status
Completed

Conditions

  • Breast Cancer
  • Early-Stage Breast Carcinoma
  • Human Epidermal Growth Factor 2 Negative Carcinoma of Breast

Eligibility Criteria

Sex
FEMALE
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • ME-344 — DRUG
    ME-344 is a synthetic small molecule mitochondrial inhibitor based on the isoflavan ring structure. ME-344 is a chiral compound, and is manufactured predominantly as a single stereoisomer that is dextrorotatory. As a stereoisomeric drug with two chiral centers, ME-344 is one of four potential stereoisomers. The current manufacturing process produces a racemic mixture of two of those stereoisomers, which are enantiomers, and ME-344 is separated from the levorotatory enantiomer by chromatography in the final step.
  • Bevacizumab — DRUG
    Bevacizumab is a recombinant humanized monoclonal antibody that blocks angiogenesis by inhibiting vascular endothelial growth factor A (VEGF-A)
  • Normal saline — OTHER
    Use saline as placebo

Study Details

Prospective, randomized, open label, two arms,, phase 0 clinical trial. HER2-negative breast cancer patients recently diagnosed will be screened for trial participation. A biopsy will be scheduled the week prior to or the same day as the FDG PET. Paraffin-embedded tumor samples will be used to evaluate the stainings of Ki67, cleaved caspase-3 and microvessels, and frozen tumor samples will be used to evaluate SDH staining. The FDG-PET will be followed by the bevacizumab dose (15 mg/kg IV, single dose). After one week, the PET will be repeated in order to detect the patients that have experienced FDG uptake decay. Right after, treatment with ME-344 (arm 1) or no treatment (arm 2) will start. ME-344 will be administered at 10 mg/kg on day 8, 15 and 22. Surgery will be performed on day 28 (thus, 4 weeks after the bevacizumab dose, which is considered a safe window for antiangiogenics). Fragments of the surgical specimen will be collected. Paraffin-embedded tumor sample will be used to repeat (and compare) the stainings of Ki67, cleaved caspase-3 and microvessels, and frozen tumor sample will be used to repeat (and compare) SDH staining. Patients will come off trial in case of consent withdrawal, unequivocal disease progression is observed, unacceptable toxicity occurs, or in case of intercurrent disease or any other condition deemed incompatible with continuation in the clinical trial by the investigator.

Key Dates

First listed
Jun 21, 2016
Start date
Jul 31, 2016
Status verified
Jul 2019
Primary completion
Oct 31, 2018
Completion
Nov 30, 2018

Study Design

Enrollment
40 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE

Arms

  • Experimental: Bevacizumab + ME-344
    Bevacizumab single dose (15 mg/kg infused IV) on day 1. ME-344 will be administered at 10 mg/kg infused IV over 30 minutes on days 8, 15 and 22 (arm 1). ME-344 will be suspended in 250 mL sterile saline.
  • Placebo Comparator: Bevacizumab + normal saline
    Bevacizumab single dose (15 mg/kg infused IV) on day 1. Placebo: will be administered normal saline 250 mL infused IV over 30 minutes on days 8, 15 and 22 (arm 2).

Primary Outcome Measure

Reduction of FDG uptake [ Time Frame: 1 month ]

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